The use of immortalised cell lines has become indispensable in understanding human disease and accelerating drug discovery. Unlike animal models, which raise concerns about translatability, or primary cells, which have short lifespans, immortalised cell lines provide a renewable, consistent, and cost-effective resource for research. They capture essential biological processes while allowing laboratories worldwide to reproduce findings with reliability.
This article explores ten widely studied lines, each contributing uniquely to biomedical science by enabling disease modelling, therapeutic evaluation, and mechanistic studies.
HeLa Cells and the Origins of Cancer Biology
The establishment of HeLa cells in the early 1950s marked a turning point in biomedical research. Derived from cervical carcinoma, they were the first human cells capable of indefinite proliferation, offering researchers an unprecedented tool to explore cancer biology.
HeLa cells facilitated studies into chromosomal instability, tumour suppressor genes, and oncogenic viruses such as human papillomavirus (HPV). They also provided a model for testing the effects of radiation and chemotherapy agents. Their resilience and adaptability underpinned countless cancer-related studies, laying the groundwork for therapies still in use today.
Despite their scientific value, HeLa’s history prompted discussions about informed consent and the ethical use of patient tissues. This case directly influenced how biobanking and human sample regulations are structured today.
HEK293 and the Study of Gene Function
While HeLa shaped cancer biology, HEK293 cells revolutionised gene function research. Developed in the 1970s, they are uniquely suited for transfection experiments, allowing scientists to introduce foreign DNA and study its expression.
Their impact has been profound in:
- Pharmacology, where they are used to study receptors, transporters, and ion channels.
- Gene therapy, with HEK293 lines producing viral vectors for delivering corrective genes.
- Molecular biology, where they serve as factories for recombinant protein production.
These characteristics have made HEK293 an irreplaceable model in understanding how genes control cellular behaviour and how genetic manipulation can lead to novel treatments.
CHO Cells in Industrial Biomanufacturing
Among immortalised lines, CHO cells stand out not for disease modelling but for their role in industrial biotechnology. Originating from Chinese hamster ovary tissue, they are used almost exclusively in large-scale production of therapeutic proteins.
CHO cells became essential because they:
- Thrive in suspension cultures, allowing bioreactor-based mass production.
- Tolerate serum-free environments, minimising contamination risks.
- Generate human-compatible glycosylation patterns, ensuring therapeutic proteins are effective and safe.
The majority of monoclonal antibody therapies and several recombinant hormones are manufactured using CHO-based systems. Without them, the pharmaceutical industry could not meet global demand for biologics.
SH-SY5Y and Modelling Neurodegeneration
For neuroscience, SH-SY5Y cells have become a standard for modelling neuronal function. Derived from neuroblastoma, they can be chemically induced to differentiate into neuron-like cells, forming axons and synapses.
Researchers employ SH-SY5Y cells to study:
- Parkinson’s disease, by analysing dopamine metabolism and mitochondrial dysfunction.
- Alzheimer’s disease, through experiments on amyloid precursor protein and tau phosphorylation.
- Drug screening, where candidate compounds are tested for neuroprotection or neurotoxicity.
Although they cannot fully replicate the diversity of human neurons, their adaptability offers a scalable alternative to primary brain tissue, which is often limited in availability.
MCF7 as a Model for Hormone-Dependent Tumours
The MCF7 breast cancer line provides an invaluable system for studying hormone-dependent cancers. Retaining oestrogen receptor expression, these cells are used to explore the role of endocrine pathways in tumour development and progression.
Research with MCF7 has contributed to:
- Understanding how oestrogen signalling drives cancer proliferation.
- Exploring mechanisms of resistance to anti-oestrogen drugs like tamoxifen.
- Testing the cytotoxicity of chemotherapeutics in ER-positive tumours.
Their reliability and responsiveness have made MCF7 a reference point in preclinical oncology, particularly in trials involving hormone-targeted treatments.
THP1 and the Complexity of Immunity
The immune system is complex and difficult to model, but THP1 cells provide a reproducible system for investigating innate immunity. Derived from acute monocytic leukaemia, THP1 cells can differentiate into macrophage-like cells, enabling controlled study of immune responses.
They are especially valuable for:
- Identifying cytokine pathways activated by pathogens or toxins.
- Investigating the impact of nanoparticles on immune regulation.
- Testing immunomodulatory drugs before animal or human trials.
Although not a substitute for the full complexity of the human immune system, THP1 cells offer insights into inflammation and host–pathogen dynamics, helping refine immunological hypotheses.
A2780 and the Challenge of Drug Resistance
The ovarian carcinoma line A2780 is central to oncology because it models the sensitivity and resistance of tumours to chemotherapy, especially platinum-based compounds.
Through A2780 studies, researchers have:
- Identified resistance mechanisms involving DNA repair enzymes and efflux pumps.
- Developed drug combinations that improve treatment efficacy.
- Tested experimental compounds to overcome therapy failure.
Since ovarian cancer remains difficult to treat in advanced stages, A2780 continues to be a valuable platform for designing novel approaches that address chemoresistance.
HL-60 and the Exploration of Blood Cell Differentiation
Promyelocytic HL-60 cells have contributed extensively to our understanding of blood cancers and differentiation. Established from acute promyelocytic leukaemia, they can mature into granulocytic or monocytic forms depending on stimuli.
Their contributions include:
- Elucidating the role of retinoic acid in differentiation therapies.
- Providing a model for studying apoptosis in myeloid cells.
- Supporting toxicological assessments of environmental agents affecting haematopoiesis.
HL-60 cells illustrate how immortalised lines can illuminate both the pathology of leukaemia and pathways leading to therapeutic interventions.
Caco-2 and Drug Absorption Studies
The colon carcinoma-derived Caco-2 line plays a vital role in drug development pipelines. When cultured over time, these cells mimic enterocyte-like functions, including formation of tight junctions and expression of transport proteins.
Their utility includes:
- Predicting oral bioavailability of drugs through permeability assays.
- Assessing nutrient absorption in nutritional sciences.
- Investigating the impact of microbiota metabolites on gut epithelium.
Because they closely resemble intestinal barriers, Caco-2 assays are frequently used by regulatory agencies when evaluating new pharmaceuticals.
HepG2 and the Study of Liver Function
The HepG2 hepatocellular carcinoma line remains a principal model for liver function studies. While they lack the full metabolic capacity of primary hepatocytes, their reproducibility and ease of maintenance make them ideal for high-throughput experiments.
HepG2 cells are employed in:
- Toxicology screening to detect hepatotoxic side effects of new drugs.
- Metabolism research, including lipid processing and glucose regulation.
- Virology studies, particularly those involving hepatitis viruses.
Despite limitations, their stability ensures they remain one of the most commonly used hepatic models, bridging laboratory research and preclinical toxicology.
Conclusion
From the immortal HeLa line that shaped cancer research to the biomanufacturing powerhouse of CHO, immortalised cell lines continue to drive advances in medicine and biotechnology. HEK293 enables precise gene manipulation, SH-SY5Y models neurological conditions, MCF7 advances breast cancer treatment, THP1 provides an immune system proxy, and A2780 highlights the complexity of drug resistance. HL-60 illuminates differentiation pathways, Caco-2 predicts drug absorption, and HepG2 supports hepatology and toxicology studies.
Together, these models provide a framework for understanding disease mechanisms, improving therapies, and ensuring that discoveries made in the laboratory can be translated into clinical reality. While they cannot perfectly replicate the intricacies of human physiology, their collective impact on science is undeniable, and their refinement will continue to shape the future of biomedical research.